In this paper, we unveil the electronic structure of the highest occupied and lowest excited unoccupied molecular frontier orbitals in semiconducting bisacene thin films. Thin films of angularly fused bisacenes, namely, pentaceno-pentacene, pentaceno-hexacene, and hexaceno-hexacene, are obtained after the thermal conversion of the spin-coated thin films prepared from highly concentrated ink of precursor molecules. Thus, by a combination of electron spectroscopies, namely, valence band photoemission and near-edge X-ray absorption fine structure spectroscopy, we are able to characterize the occupied and excited unoccupied density of states of the molecular frontier orbitals. We demonstrate that, under specific assumptions, it is possible to combine valence band spectra and absorption spectra relative to the Fermi level and derive the transport gap of angularly fused bisacene films relative to those of pentacene. Both the electronic structure of the frontier orbitals and the transport gap of a pentaceno-pentacene film are found alike as a pentacene film. This demonstrates that, in thin films, the delocalized character of the electrons along the angularly fused bisacene is limited to the acene subunit and adopts the pentacene electronic structure. Because of the high solubility of the bisacene precursors, it can be foreseen as a promising alternative to pentacene precursors, which exhibit poor solubility.

Prostate-specific membrane antigen (PSMA) radioligand therapy is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC). Several beta or alpha particle-emitting radionuclide-conjugated small molecules have shown efficacy in late-stage mCRPC and one, [[177Lu]Lu]Lu-PSMA-617, is FDA approved. In addition to tumor upregulation, PSMA is also expressed in kidneys and salivary glands where specific uptake can cause dose-limiting xerostomia and potential for nephrotoxicity. The PSMA inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) can prevent kidney uptake in mice, but also blocks tumor uptake, precluding its clinical utility. Preferential delivery of 2-PMPA to non-malignant tissues could improve the therapeutic window of PSMA radioligand therapy. A tris(isopropoxycarbonyloxymethyl) (TrisPOC) prodrug of 2-PMPA, JHU-2545, was synthesized to enhance 2-PMPA delivery to non-malignant tissues. Mouse pharmacokinetic experiments were conducted to compare JHU-2545-mediated delivery of 2-PMPA to plasma, kidney, salivary glands, and C4-2 prostate tumor xenograft. Imaging studies were conducted in rats and mice to measure uptake of PSMA PET tracers in kidney, salivary glands, and prostate tumor xenografts with and without JHU-2545 pre-treatment. JHU-2545 resulted in approximately 3- and 53-fold greater exposure of 2-PMPA in rodent salivary glands (18.0 ± 0.97 h*nmol/g) and kidneys (359 ± 4.16 h*nmol/g) versus prostate tumor xenograft (6.79 ± 0.19 h*nmol/g). JHU-2545 also blocked rodent kidneys and salivary glands uptake of the PSMA PET tracers [68Ga]Ga-PSMA-11 and [18 F]F-DCFPyL by up to 85 Pertinent findings: JHU-2545, a prodrug of the PSMA inhibitor 2-PMPA, was found to preferentially deliver 2-PMPA to salivary glands and kidneys relative to tumor xenografts in rodent models, leading to blunted uptake of PSMA radioligands in non-tumor tissues. Implications for patient care: If replicated in clinical studies, JHU-2545 could reduce radiation doses to salivary glands and kidneys and possibly mitigate associated toxicities in prostate cancer patients receiving PSMA radioligand therapy.

Helicenes are very attractive chiral non-planar polycyclic aromatic hydrocarbons possessing strong chiroptical properties. However, most of the helicenes absorb light mainly in the ultraviolet region, with only a small segment in the blue part of the visible spectrum. Furthermore, carbo[n]helicenes exhibit only weak luminescence that limits their utilization. Herein, we demonstrate that peripheral decoration of the helicene backbone with an aryl-carbonyl group shifts the absorption to the visible region and simultaneously improves their fluorescence quantum yields. We thus show that the carbonyl group, commonly considered as detrimental to emission, has the capability of improving optical and photophysical properties. Two different families, aceno[n]helicenones and fluoreno[n]helicenes, are presented with comprehensive spectrochemical characterization. TD-DFT calculations were implemented to clarify their electronic profiles. We show that increasing the helical length in aceno[n]helicenes increases absorption onset, g(abs) and g(lum). Extension of the peripheral aromatic part in fluoreno[n]helicenes leads to a blue shift in both absorption and emission.

Helicenes and helicenoid structures are promising candidates for future applications exploiting circularly polarized light. Ideal candidates should possess near-quantitative photoluminescence quantum yield, a high luminescence dissymmetry factor and an adjustable HOMO-LUMO gap. However, carbo[n]helicenes are poorly luminescent compounds and they absorb light mainly in the ultraviolet region. Here we show that the incorporation of a carbonyl group into helical scaffold significantly improves the fluorescence quantum yield and shifts the absorption to visible region. Although the carbonyl group is commonly considered as detrimental to efficient emission, fluorescence quantum yields up to Φ=0.43 were recorded. A straightforward synthetic approach to a highly luminescent tetraceno[6]helicenone and an aza analogue has been developed. The key step is a radical cyclization which is achieving dehydrative π-extension. The aza-analogue was incorporated as an emitter in organic light emitting diodes (OLEDs) and showed good performance.

The development of functional organic molecules requires structures of increasing size and complexity, which are typically obtained by the covalent coupling of smaller building blocks. Herein, with the aid of high-resolution scanning tunneling microscopy/spectroscopy and density functional theory, the coupling of a sterically demanded pentacene derivative on Au(111) into fused dimers connected by non-benzenoid rings was studied. The diradical character of the products was tuned according to the coupling section. In particular, the antiaromaticity of cyclobutadiene as the coupling motif and its position within the structure play a decisive role in shifting the natural orbital occupancies toward a stronger diradical electronic character. Understanding these structure-property relations is desirable not only for fundamental reasons but also for designing new complex and functional molecular structures.

2,9- and 2,10-diphenylpentacene were synthesized by direct C-H borylation of ketal-protected pentacene, followed by halodeboronation, resolution of the dihalo isomers, Suzuki arylation, cleavage of the ketals and decarbonylation in the solid state. They were studied as main active components in organic field effect transistors (OFETs). Diphenyl substitution of pentacene affects the unit cell dimensions only slightly, preserving a face to edge molecular packing in the first layers of thin films evaporated on SiO2 substrates. Both isomers self-assemble into nanoribbons during the thin film growth upon vapor deposition. The similarity between the surface induced phases of the 2,9-isomer and unsubstituted pentacene leads to similar 4-probe hole mobilities, i. e. 0.13 cm2 V-1 s-1 for the former. Whereas 2,9-disubstitution thus does essentially preserve the thin film characteristics of unsubstituted pentacene, 2,10-disubstitution is detrimental to the molecular ordering in the thin films and therefore to the field effect mobility which is only 0.07 cm2 V-1 s-1. The known strong enhancement of field effect mobility observed upon diphenyl substitution of anthracene can thus not be emulated analogously with pentacene.

Nonaqueous capillary electrophoresis (NACE) using methanol (MeOH) as a solvent of the BGEs and quantum mechanical density functional theory (DFT) have been applied to determine the thermodynamic acidity (ionization) constants (pK(a)) of mono- and diaza[5]helicenes, mono- and diaza[6]helicenes, and their dibenzo derivatives in MeOH and water. First, the mixed acidity constants, pKa,MeOHmix, of ionogenic pyridinium groups of azahelicenes and their derivatives in MeOH were obtained by nonlinear regression analysis of pH dependence of their effective electrophoretic mobilities. The effective mobilities were measured by NACE in a large series of methanolic BGEs within a wide conventional pH range (pH(MeOH) 1.6-12.0) and at ambient temperature (21-26 degrees C) in a home-made CE device. Prior to mixed acidity constant calculation, the effective mobilities were corrected to reference temperature (25 degrees C) and constant ionic strength (25 mM). Then, the mixed acidity constants were recalculated to the thermodynamic acidity constants pK(a,MeOH) by the Debye-Huckel theory of nonideality of electrolyte solutions. Finally, from the methanolic thermodynamic pK(a,MeOH) values, the aqueous thermodynamic pKa,H2O constants were estimated using the empirical relations between methanolic and aqueous acidity constants derived for structurally related pyridine derivatives. Depending on the number and position of the nitrogen atoms in their molecules, the analyzed azahelicenes were found to be weak to moderate bases with methanolic pK(a,MeOH) in the range 2.01-8.75 and with aqueous pKa,H2O in the range 1.67-8.28. The thermodynamic pK(a,MeOH) obtained by the DFT calculations were in a good agreement with those determined experimentally by NACE.

During the last years we have witnessed progressive evolution of preparation of acenes with length up to dodecacene by on-surface synthesis in UHV or generation of acenes up to decacene in solid matrices at low temperatures. While these protocols with very specific conditions produce the acenes in amount of few molecules, the strategies leading to the acenes in large quantities dawdle behind. Only recently and after 70 years of synthetic attempts, heptacene has been prepared in bulk phase. However, the preparative scale synthesis of higher homologues still remains a formidable challenge. Here we report the preparation and characterisation of nonacene and show its excellent thermal and in-time stability.

Acenes, polyaromatic hydrocarbons composed of linearly fused benzene rings have received immense attention due to their performance as semiconductors in organic optoelectronic applications. Their appealing physicochemical properties, such as extended delocalization, high charge carrier mobilities, narrow HOMO-LOMO gaps and partially radical character in the ground state make them very attractive targets for many potential applications. However, the intrinsic synthetic challenges of unsubstituted members such as high reactivity and poor solubility are still limiting factors for their wider exploitation. Herein, we report a simple general synthesis of a new family of angularly fused acenoacenes with improved stability compared to their isoelectronic linear counterparts. The synthesis and comprehensive characterization of pentacenopentacene, pentacenohexacene and hexacenohexacene, with lengths between decacene and dodecacene, are disclosed.

A red star is born A new route for the preparation of large and insoluble molecular starphenes by decarbonylation of soluble precursors in the solid state is described in the Research Article on page 7752 by Andrej Jancarik, Andre Gourdon, and co-workers. Scanning tunneling microscopy/spectroscopy in ultrahigh vacuum and absorption spectroscopy in frozen matrices, with both experiments run at liquid helium temperature, show that the electronic delocalization among the three pentacene branches is rather limited.

The Cover Feature shows the evolution of scanning tunneling microscopy images during the cyclodehydrogenation of a polyaromatic hydrocarbon precursor sublimated onto an Au(111) surface under ultra-high vacuum. This strategy allows the on-surface preparation and study of planar large and dissymmetric starphenes that could not be prepared in solution, and may give access to families of molecular logic gates that are of interest in single-molecule electronics. More information can be found in the Full Paper by A. Jancarik, A. Gourdon, F. Moresco, and co-workers.

A large dissymmetric starphene molecule, the tetrabenzo[a,c,u,w]naphtho[2,3-l]nonaphene, was obtained by first preparing a soluble precursor which was then sublimated on a Au(111) surface in an ultra-high vacuum. In a second step, controlled annealings from 200 °C to 275 °C initiated two successive cyclodehydrogenation steps with the formation of 3 new carbon-carbon bonds. A second conformer was also stable enough during the annealing step to give another compound in similar yield, the benzodibenzo[7,8,9,10]naphthaceno[2,1-h]phenanthro[9,10-p]hexaphene. The formation of this more-hindered species stresses the importance of strong molecule-surface interactions during the cyclodehydrogenations steps of these large polyaromatic hydrocarbons.

Starphenes are attractive compounds due to their characteristic physicochemical properties that are inherited from acenes, making them interesting compounds for organic electronics and optics. However, the instability and low solubility of larger starphene homologs make their synthesis extremely challenging. Herein, we present a new strategy leading to pristine [16]starphene in preparative scale. Our approach is based on a synthesis of a carbonyl-protected starphene precursor that is thermally converted in a solid-state form to the neat [16]starphene, which is then characterised with a variety of analytical methods, such as 13C CP-MAS NMR, TGA, MS MALDI, UV-Vis and FTIR spectroscopy. Furthermore, high-resolution STM experiments unambiguously confirm its expected structure and reveal a moderate electronic delocalisation between the pentacene arms. Nucleus-independent chemical shifts NICS(1) are also calculated to survey its aromatic character.

The tetraene 7,7‐dimethoxy‐2,3,5,6‐tetramethylenebicyclo[2.2.1]heptane is a key compound for the preparation of a large variety of acenes protected by a carbonyl bridge. We report herein a medium scale preparation in seven steps of this valuable starting material. Diels–Alder addition between 6,6‐dimethtyl fulvene and maleic anhydride, followed by carboxylation, ozonolysis of the double bond, reduction of the four ester groups, then chlorination of the alcohol groups and dehydrochlorination give the target compound in 17 % overall yield.

Surface-assisted synthesis has become a powerful approach for generation of molecular nanostructures, which could not be obtained via traditional solution chemistry. Nowadays there is an intensive search for reactions that could proceed on flat surfaces in order to boost the versatility and applicability of synthesized nano-objects. Here we propose application of atomic hydrogen combined with on-surface synthesis in order to tune the reaction pathways. We demonstrate that atomic hydrogen could be widely applied: (1) as a cleaning tool, which allows removal of halogen residues from the surface after Ullmann couplings/polymerization, (2) by reaction with surface organometallics to provide stable hydrogenated species, and (3) as a reagent for debromination or desulfurization of adsorbed species.

A versatile asymmetric synthesis of five C2 symmetric enantio‐ and diastereopure bioxa[5]‐ and bioxa[6]helicene 2,2′‐bipyridines was developed. It relied either on a double intramolecular [2+2+2] cycloisomerization of dicyanotetrayne (forming simultaneously the 2,2′‐bipyridine unit and biazaoxahelicene backbone) or one‐pot/sequential intramolecular [2+2+2] cycloisomerization of triyne accompanied by an intermolecular haloazaoxahelicene reductive homocoupling. We reached an effective central‐to‐helical‐to‐axial chirality transfer that was controlled by the 1,3‐allylic‐type strain and sterically constricted atropoisomerization of the embedded 2,2′‐bipyridine unit. The chiroptical properties of the bioxahelicene 2,2′‐bipyridines were studied along with their fluorescence properties.

Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy as an anticancer agent. The use of MBZ for cancer, however, is challenging due to its poor solubility leading to poor bioavailability. Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics. Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility. When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph. In dogs, 12 showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C. In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.

Production of nitro compounds has only seldom been recorded in arthropods. The aliphatic nitroalkene (E)-nitropentadec-1-ene (NPD), identified in soldiers of the termite genus Prorhinotermes, was the first case documented in insects in early seventies. Yet, the biosynthetic origin of NPD has long remained unknown. We previously proposed that NPD arises through the condensation of amino acids glycine and/or l-serine with tetradecanoic acid along a biosynthetic pathway analogous to the formation of sphingolipids. Here, we provide a metabolomics and transcriptomic data of the Prorhinotermes simplex termite workers and soldiers. Data are related to NPD biosynthesis in P. simplex soldiers. Original metabolomics data were deposited in MetaboLights metabolomics database and are become publicly available after publishing the original article. Additionally, chemical synthesis of biosynthetic intermediates of NPD in nonlabeled and stable labeled forms are reported. Data extend our poor knowledge of arthropod metabolome and transcriptome and would be useful for comparative study in termites or other arthropods. The data were used for de-replication of NPD biosynthesis and published separately (Jirošová et al., 2017) [1].